As society strives to produce more effective medicines, cosmetics and other industrial materials, while at the same time minimising the effect on the environment and the depletion of the earth's resources, one major source of renewable natural materials has remained tantalisingly beyond our reach: the deepest, most inaccessible and hostile parts of the ocean. MAMBA is a pioneering European Union (EU)-funded research project, which is changing that.
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The research team is extending the frontiers of our capabilities, making it possible to harvest the vast resources offered by the enzymes, proteins and other molecules contained in the microbial life which exists in the harshest marine environments – at the extremes of heat, cold, pressure and salinity. The highly adapted cellular machinery required to survive in these extreme conditions is the reason these organisms are of special interest. The molecules they contain are likely to have properties not found in organisms existing in more common habitats.
“Microbes have a great potential for biotechnology,” says MAMBA’s Project Coordinator, Professor Peter Golyshin of Bangor University in the United Kingdom. “Micro-organisms have been found to be particularly suitable for production of compounds with anti-inflammatory, anti-bacterial, anti-fungal, cholesterol-lowering and anti-cancer activity, as well as enzymes applicable in the food, cosmetics and pharmaceuticals industries.”
Even more importantly, the sea is the most promising source of such microbes. “Marine microbial communities are thought to contain anti-tumour potential at least 100 times higher than terrestrial microbes,” says Professor Golyshin. “In addition, the deep ocean realms, particularly below 1,000 metres in depth, are by far the least explored systems on Earth,” he adds.
Until now, the problem has been the difficulty of creating laboratory cultures of these microbes in order to study them and realise the potential benefits they offer. This is because most micro-organisms form partnerships with other micro- or higher organisms in their environment. If they are extracted from this environment they may lack some essential factors they need in order to grow. For this reason, less than a fraction of one per cent of the total number of microbial species that are detected in nature has been successfully cultured.
The key to the success of the MAMBA project was the use of techniques from the rapidly developing science of ‘metagenomics’. Metagenomics applies genetic methods not to the study of the genome of a single organism, but to the study of all the genetic material contained in an environmental sample. By harvesting genes from microbial communities directly from the environment - something now made possible by modern metagenomic techniques - it is possible to bypass the need for the isolation and laboratory cultivation of individual species.
The activities of the MAMBA team have been likened to those of prospectors for mineral wealth, except that in this case the prospectors are searching the seas for ‘biological wealth’. Their success rate has been impressive. More than four million clones have been screened to yield some 1,600 positive hits exhibiting the desired enzymatic activity, from which two hundred enzymes have been fully characterised. In particular, the project has more than doubled the number of known protein structures from organisms adapted to cold conditions.
“The biocatalysts developed as a result of MAMBA’s work,” explains Professor Golyshin, “have applications ranging from pharmaceutical production to cosmetic design, food production, bio-energy production and the production of valuable fine chemicals.”
As well as paving the way for a wealth of new medicines, cosmetics and other products, the MAMBA project is also expected to help environmental sustainability by boosting the ‘white biotechnology’ approaches to production, using renewable raw biological material as feedstock.
“The fruits of MAMBA’s pioneering work could be in evidence very soon,” says Professor Golyshin. While new drug development will of course take many years to progress through all the necessary regulatory stages, the exploitation of enzymes in industry can be expected much sooner. “Currently, hundreds of MAMBA enzymes are being tested in collaboration with private companies and we expect to have some of the enzymes in commercial portfolios within the next two to three years,” he concludes.